1. Field of the Invention
The present invention relates to a medical device for use in tissue and organ treatment and, in particular, to drug-loaded microparticles embedded within a matrix and applied to the medical device.
2. Related Art
A variety of surgical procedures and medical devices are currently used to relieve intraluminal constrictions caused by disease or tissue trauma. An example of one such procedure is percutaneous transluminal coronary angioplasty (PTCA). PTCA is a catheter-based technique whereby a balloon catheter is inserted into a blocked or narrowed coronary lumen of the patient. Once the balloon is positioned at the blocked lumen or target site, the balloon is inflated causing dilation of the lumen. The catheter is then removed from the target site thereby allowing blood to freely flow through the unrestricted lumen.
Although PTCA and related procedures aid in alleviating intraluminal constrictions, such constrictions or blockages reoccur in many cases. The cause of these recurring obstructions, termed restenosis, is due to the body""s immune system responding to the trauma of the surgical procedure. As a result, the PTCA procedure may need to be repeated to repair the damaged lumen.
Stents or drug therapies, either alone or in combination with the PTCA procedure, are often used to avoid or mitigate the effects of restenosis at the surgical site. In general, stents are small, cylindrical devices whose structure serves to create or maintain an unobstructed opening within a lumen. The stents are typically made of stainless steel or a memory-responsive metal, such as Nitinol(trademark) and are delivered to the target site via a balloon catheter. Although the stents are effective in opening the stenotic lumen, the foreign material and structure of the stents themselves may exacerbate the occurrence of restenosis or thrombosis.
Drugs or similar agents that limit or dissolve plaque and clots are used to reduce, or in some cases eliminate, the incidence of restenosis and thrombosis. Since the drugs are applied systemically to the patient, they are absorbed not only by the tissues at the target site, but by all areas of the body. As such, one drawback associated with the systemic application of drugs is that areas of the body not needing treatment are also affected. To provide more site-specific treatment, stents are frequently used as a means of delivering the drugs exclusively to the target site. By positioning the stent at the target site, the drugs can be applied directly to the area of the lumen requiring therapy or diagnosis.
In addition to the benefit of site-specific treatment, drug-loaded stents also offer long-term treatment and/or diagnostic capabilities. These stents include a biodegradable or absorbable polymer suspension that is saturated with a particular drug. In use, the stent is positioned at the target site and retained at that location either for a predefined period or permanently. The polymer suspension releases the drug into the surrounding tissue at a controlled rate based upon the chemical and/or biological composition of the polymer and drug.
The above-described devices and methods for treatment of restenosis and thrombosis, and other similar conditions not specifically described, offer many advantages to potential users. However, it has been discovered that such devices and methods may be deficient in their current drug-loading and drug-delivery characteristics. In particular, the amount or volume of drug capable of being delivered to the target site may be insufficient due to the limited surface area of the stent. In addition, drug release rates may also be inadequate since the rate at which the drug is released or delivered to the target site is a function of the chemical and/or biological properties of the polymer in which the drug is embedded.
In view of the above, it is apparent that there is a need to provide a drug delivery device offering increased drug loading capabilities for medical devices and improved drug release rates. It is also desirable that the drug-delivery device allows one or more drugs to be released from the medical device to the target site. In addition, it is preferred that the device features enable one or more drugs to be released at variable and/or independent rates. There is also a need to provide a method of manufacturing such an improved drug delivery device that is convenient, efficient and cost effective.
In accordance with various aspects of the present invention, a small particle, such as a micro- and/or nanoparticle (hereinafter referred to interchangeably as xe2x80x9cmicroparticlexe2x80x9d), is formed and loaded with a drug. The drug-loaded microparticle is formulated by combining a drug with various chemical solutions. In one embodiment, a microparticle can be formed by adding a drug-loaded solution containing a photoinitiator into a relatively inert bath. Light or similar energy is applied to the solution in the bath causing a photo-chemical reaction that produces one or more microparticles. In another embodiment, the drug-loaded solution is combined with a cross-linker solution and vigorously vortexed in a inert bath. The agitation together with the chemical reaction produces one or more microparticles. Specified sizes of the microparticles and amounts of drug(s) contained within the microparticles may be varied by altering the proportions of the above chemicals/solutions and by varying the process parameters during mixing. In addition to various drugs, therapeutic substances and radioactive isotopes may also be loaded into the microparticles.
Another aspect of the present invention is a method of applying a drug-loaded microparticle onto a medical device. A microparticle can be formed and loaded with one or more drugs, as described above. The drug-loaded microparticle is suspended in a polymer solution forming a polymer matrix. In one embodiment, the medical device is dipped in the polymer matrix so that a coating of the polymer matrix having a relatively smooth surface texture is applied over the entire surface of the medical device. In another embodiment, the entire surface of the medical device is spray coated with the polymer matrix. In yet another embodiment, only select portions of the medical device are coated with one or more polymer matrices.
Embodiments of the medical device make possible site specific treatment therapies. Coating different portions of an implantable medical device, with the disclosed microparticles loaded with various drugs advantageously allows site-specific treatment of discrete sections of the patient""s lumen. In addition, by embedding the drug-loaded microparticle in a polymer, the resulting matrix can increase or decrease the release rate of the drug from the microparticle, depending on the type of polymer used. As such, drug release rates and thereby, for example, long term treatment or diagnostic capabilities, can be controlled. Moreover, the drugs can be suspended in a tissue-compatible polymer, such as silicone, polyurethane, polyvinyl alcohol, polyethylene, polyesters, swellable hydrogels, hyaluronate, various copolymers and blended mixtures thereof. Accordingly, a very selective cushioning effect can be attained.